Long-term, all-cause mortality risk after infection episodes in older adults
Authors: Max Carlos Ramírez-Soto
Journal: The Lancet Healthy Longevity (2023)

Infectious diseases are among the top 20 causes of death in adults over the age of 60 years worldwide.1WHOMortality rate in older adults—top 20 causes (global and regions). World Health Organization.https://www.who.int/data/maternal-newborn-child-adolescent-ageing/indicator-explorer-new/mca/mortality-rate-in-older-people---top-20-causes-(global-and-regions)Date accessed: July 31, 2023Google Scholar Various studies have reported an increased risk of short-term and long-term mortality following bloodstream infection, sepsis, or pneumonia.2Nielsen SL Lassen AT Gradel KO et al.Bacteremia is associated with excess long-term mortality: a 12-year population-based cohort study.J Infect. 2015; 70: 111-126Summary Full Text Full Text PDF PubMed Google Scholar, 3Leibovici L Samra Z Konigsberger H Drucker M Ashkenazi S Pitlik SD Long-term survival following bacteremia or fungemia.JAMA. 1995; 274: 807-812Crossref PubMed Google Scholar, 4Dick A Liu H Zwanziger J et al.Long-term survival and healthcare utilization outcomes attributable to sepsis and pneumonia.BMC Health Serv Res. 2012; 12: 432Crossref PubMed Scopus (45) Google Scholar All-cause mortality (after 1 year or more) following a bloodstream infection has been reported to range from 8% to 48%, with the relative risk of death at 1 year estimated at 4·04 (95% CI 1·84–8·87), according to a 2018 systematic review.5McNamara JF Righi E Wright H Hartel GF Harris PNA Paterson DL Long-term morbidity and mortality following bloodstream infection: A systematic literature review.J Infect. 2018; 77: 1-8Summary Full Text Full Text PDF PubMed Scopus (46) Google Scholar However, that systematic review did not analyse mortality in older adults, nor did it consider other causes of infection or longer follow-up periods. Previous research in older adults has shown that postoperative infections, such as bloodstream infection, surgical site infection, urinary tract infection, pneumonia, and two, three, or multiple types of infection are associated with low survival rates and with increased risk of mortality after 1 year.6O'Brien WJ Gupta K Itani KMF Association of postoperative infection with risk of long-term infection and mortality.JAMA Surg. 2020; 155: 61-68Crossref PubMed Scopus (25) Google Scholar Specific infections, such as bloodstream infections caused by Gram-negative bacteria and respiratory syncytial virus pneumonia, are also associated with higher mortality rates in older adults.2Nielsen SL Lassen AT Gradel KO et al.Bacteremia is associated with excess long-term mortality: a 12-year population-based cohort study.J Infect. 2015; 70: 111-126Summary Full Text Full Text PDF PubMed Google Scholar, 7McNamara JF Harris PNA Chatfield MD Paterson DL Long term sepsis readmission, mortality and cause of death following Gram negative bloodstream infection: a propensity matched observational linkage study.Int J Infect Dis. 2022; 114: 34-44Summary Full Text Full Text PDF PubMed Scopus (0) Google Scholar, 8Tseng HF Sy LS Ackerson B et al.Severe morbidity and short- and mid- to long-term mortality in older adults hospitalized with respiratory syncytial virus infection.J Infect Dis. 2020; 222: 1298-1310Crossref PubMed Scopus (0) Google Scholar Notably, in a cohort of adults aged 65 years or older with sepsis and cancer, older age and the source and severity of sepsis were not associated with mortality after 1 year.9Courtright KR Jordan L Murtaugh CM et al.Risk factors for long-term mortality and patterns of end-of-life care among Medicare sepsis survivors discharged to home health care.JAMA Netw Open. 2020; 3e200038 Crossref PubMed Scopus (18) Google Scholar Independently of the causative pathogen, long-term mortality rates (3–5 years) after bacteraemia and sepsis ranged from 37% to 49% in hospitalised adults aged 60 years or older (Francisco and colleagues, Lillie and colleagues; appendix pp 1–2). For older adults in intensive critical care, the mortality rate was higher, reaching up to 61% (Cuthbertson and colleagues; appendix pp 1–3; panel).PanelSummary of studies on short-term, mid-term, and long-term all-cause mortality after infection episodes in older adultsTypically recruited populations •Adults aged 65 years or older admitted to hospital with mild or severe infection•Adults undergoing major surgery•Adults who underwent isolated coronary artery bypass grafting•Adult sepsis survivors diagnosed with cancer•Adults or older adults in intensive care unitsAssessment of exposure: type of infection •Bloodstream infection or sepsis, urinary tract infection, pneumonia, cellulitis, cholecystitis, peritonitis, endocarditis, or meningitis•Postoperative infection (eg, bloodstream infection, surgical site infection, urinary tract infection, pneumonia, two types of infection, and three or more types of infection)•Severe sepsis (site of infection: bloodstream infection, bronchopulmonary infection, deep wound, or urinary tract infection)•Bloodstream infection after coronary surgery•Severe infection with or without sepsis criteria: sepsis, severe sepsis, or septic shock•Community-acquired pneumoniaAssessment of exposure: specific pathogens •Gram-negative bacteraemia: Escherichia coli, Enterobacter spp, Klebsiella spp, Pseudomonas aeruginosa, and anaerobic Gram-negative rods•Gram-positive bacteraemia: Staphylococcus aureus, Streptococcus pneumoniae, Hemolytic streptococci, Enterococcus spp, and coagulase-negative staphylococci•Fungaemia by Candida spp•Respiratory syncytial virus pneumoniaDuration of follow-up after infection episodes* •Short-term (≤60 days)•Mid-term (61 days to <1 year)•Long-term (1–5 years or more)Short-term, mid-term, and long-term outcomes (all-cause mortality) •Increase in the risk of mid-term and long-term mortality after postoperative infection, Gram-negative bloodstream infection, or respiratory syncytial virus pneumonia•Short-term and long-term high mortality rates after bacteraemia or fungaemia episodes•Increase in the risk of long-term mortality and high mortality rate after bloodstream infection, severe infection, severe sepsis, pneumonia, or infections after coronary surgery, including patients in an intensive care unitSee appendix (pp 1–2) for details and references. *In studies, there is no consensus on the duration of follow-up after infection episodes; these follow-up periods are according to the studies included in the appendix (pp 1–2). Typically recruited populations •Adults aged 65 years or older admitted to hospital with mild or severe infection•Adults undergoing major surgery•Adults who underwent isolated coronary artery bypass grafting•Adult sepsis survivors diagnosed with cancer•Adults or older adults in intensive care units Assessment of exposure: type of infection •Bloodstream infection or sepsis, urinary tract infection, pneumonia, cellulitis, cholecystitis, peritonitis, endocarditis, or meningitis•Postoperative infection (eg, bloodstream infection, surgical site infection, urinary tract infection, pneumonia, two types of infection, and three or more types of infection)•Severe sepsis (site of infection: bloodstream infection, bronchopulmonary infection, deep wound, or urinary tract infection)•Bloodstream infection after coronary surgery•Severe infection with or without sepsis criteria: sepsis, severe sepsis, or septic shock•Community-acquired pneumonia Assessment of exposure: specific pathogens •Gram-negative bacteraemia: Escherichia coli, Enterobacter spp, Klebsiella spp, Pseudomonas aeruginosa, and anaerobic Gram-negative rods•Gram-positive bacteraemia: Staphylococcus aureus, Streptococcus pneumoniae, Hemolytic streptococci, Enterococcus spp, and coagulase-negative staphylococci•Fungaemia by Candida spp•Respiratory syncytial virus pneumonia Duration of follow-up after infection episodes* •Short-term (≤60 days)•Mid-term (61 days to <1 year)•Long-term (1–5 years or more) Short-term, mid-term, and long-term outcomes (all-cause mortality) •Increase in the risk of mid-term and long-term mortality after postoperative infection, Gram-negative bloodstream infection, or respiratory syncytial virus pneumonia•Short-term and long-term high mortality rates after bacteraemia or fungaemia episodes•Increase in the risk of long-term mortality and high mortality rate after bloodstream infection, severe infection, severe sepsis, pneumonia, or infections after coronary surgery, including patients in an intensive care unit See appendix (pp 1–2) for details and references. *In studies, there is no consensus on the duration of follow-up after infection episodes; these follow-up periods are according to the studies included in the appendix (pp 1–2). Despite these previous findings, little is known about the longitudinal trends of cumulative infections and long-term all-cause mortality in older adults. In The Lancet Healthy Longevity, Hung-Yu Lin and colleagues10Lin H-Y Hsiao F-Y Huang S-T Chen Y-C Lin S-W Chen L-K Longitudinal impact of distinct infection trajectories on all-cause mortality of older people in Taiwan: a retrospective, nationwide, population-based study.Lancet Healthy Longev. 2023; 4: e508-e516Google Scholar add to the growing body of research on this topic by reporting on their retrospective cohort study of 79 666 adults aged 65 years or older, admitted to hospitals in Taiwan, in 2011, due to urinary tract infections, pneumonia, sepsis, cellulitis, cholecystitis, peritonitis, endocarditis, or meningitis. The authors assessed four groups of infection episodes: infrequent, increasing, decreasing, and frequent infections. Urinary tract infections were the most prevalent type of infection (40%), followed by pneumonia, cellulitis, and cholecystitis, during the 5-year follow-up period. After adjustments for age, sex, and comorbidities, Lin and colleagues found an increased risk of all-cause mortality for frequent (adjusted hazard ratio 2·96 [95% CI 2·82–3·11]), increasing (2·15 [2·09–2·22]), and decreasing infections (1·85 [1·80–1·91]), compared with people with infrequent infections. An important strength of Lin and colleagues' study10Lin H-Y Hsiao F-Y Huang S-T Chen Y-C Lin S-W Chen L-K Longitudinal impact of distinct infection trajectories on all-cause mortality of older people in Taiwan: a retrospective, nationwide, population-based study.Lancet Healthy Longev. 2023; 4: e508-e516Google Scholar is that it includes a comprehensive sample that is larger than previous prospective or retrospective cohort studies on long-term mortality after infections (appendix pp 1–2). Second, the study assessed a wide range of infections over a 5-year period. Previous cohort studies in older adults, including one systematic review, generally investigated only one or two types of infection (bacteriemia, sepsis, or pneumonia),2Nielsen SL Lassen AT Gradel KO et al.Bacteremia is associated with excess long-term mortality: a 12-year population-based cohort study.J Infect. 2015; 70: 111-126Summary Full Text Full Text PDF PubMed Google Scholar, 3Leibovici L Samra Z Konigsberger H Drucker M Ashkenazi S Pitlik SD Long-term survival following bacteremia or fungemia.JAMA. 1995; 274: 807-812Crossref PubMed Google Scholar, 4Dick A Liu H Zwanziger J et al.Long-term survival and healthcare utilization outcomes attributable to sepsis and pneumonia.BMC Health Serv Res. 2012; 12: 432Crossref PubMed Scopus (45) Google Scholar whereas another retrospective cohort study investigated the risk of 1-year mortality in patients with bloodstream infection, surgical site infection, urinary tract infections, pneumonia, two types of infection, and three or more types of infection.6O'Brien WJ Gupta K Itani KMF Association of postoperative infection with risk of long-term infection and mortality.JAMA Surg. 2020; 155: 61-68Crossref PubMed Scopus (25) Google Scholar Third, the study design is robust because all infection episodes were included in analytical models that captured the longitudinal mortality risk in four groups with different infection trajectories. This study also has some limitations. First, although the authors obtained a large amount of data by identifying patients from Taiwan's National Health Insurance, the study's retrospective nature makes it subject to bias due to inaccuracies in the data. Second, the mortality risk by infection type or site was not assessed in this study, regardless of infection cumulative trajectory groups. Although the authors' findings are remarkable, they included highly prevalent infections that tend to be non-lethal, such as urinary tract infection. However, several studies have reported that more serious infections such as bacteraemia, pneumonia, endocarditis, or sepsis can increase the long-term mortality risk in older adults (panel). Third, the data source used by Lin and colleagues did not include any data on laboratory tests, which hinders assessment of longitudinal trajectories of infection by specific pathogens. However, cohort studies have reported an increased risk of mortality 1 year after respiratory syncytial virus infection, or 5 years after Gram-negative and Gram-positive bactaeremia (panel).2Nielsen SL Lassen AT Gradel KO et al.Bacteremia is associated with excess long-term mortality: a 12-year population-based cohort study.J Infect. 2015; 70: 111-126Summary Full Text Full Text PDF PubMed Google Scholar, 7McNamara JF Harris PNA Chatfield MD Paterson DL Long term sepsis readmission, mortality and cause of death following Gram negative bloodstream infection: a propensity matched observational linkage study.Int J Infect Dis. 2022; 114: 34-44Summary Full Text Full Text PDF PubMed Scopus (0) Google Scholar, 8Tseng HF Sy LS Ackerson B et al.Severe morbidity and short- and mid- to long-term mortality in older adults hospitalized with respiratory syncytial virus infection.J Infect Dis. 2020; 222: 1298-1310Crossref PubMed Scopus (0) Google Scholar Considering the changing epidemiological circumstances around the COVID-19 pandemic; the high rate of hospitalisations and severe outcomes associated with pneumonia that develops from SARS-CoV-2, influenza, and respiratory syncytial virus infection; epidemiological dynamics of the COVID-19 pandemic; and the growing antimicrobial resistance of pathogens causing sepsis, endocarditis, peritonitis, or meningitis, further studies are needed to better understand cumulative longitudinal infection trajectories and their severity by infection type and specific pathogens. Furthermore, most previous studies have been done in middle-income or high-income countries, providing data that might not accurately reflect the realities in some low-income and middle-income countries (which tend to face greater challenges in health-care access and where deaths by specific infectious causes might be underreported). Hence, assessing whether cumulative longitudinal trajectories of infections increase long-term mortality risk in low-income and middle-income countries is necessary, because this association could differ by level of economic development. In summary, Lin and colleagues' study10Lin H-Y Hsiao F-Y Huang S-T Chen Y-C Lin S-W Chen L-K Longitudinal impact of distinct infection trajectories on all-cause mortality of older people in Taiwan: a retrospective, nationwide, population-based study.Lancet Healthy Longev. 2023; 4: e508-e516Google Scholar provides robust results regarding associations between longitudinal infection burden and all-cause mortality. Their findings show that multiple infection episodes, including less lethal infections, contribute to an increased risk of all-cause mortality after 5 years. The adverse effects from these infections seem to accumulate over time, increasing susceptibility and frailty in older adults and endangering their health. Such findings can be used in clinical practice to implement infection-prevention strategies and effective care interventions and risk communication to improve the health of older adults. I declare no competing interests. Download .pdf (.24 MB) Help with pdf files Supplementary appendix Longitudinal impact of distinct infection trajectories on all-cause mortality of older people in Taiwan: a retrospective, nationwide, population-based studyOlder adults with multiple infection episodes, irrespective of type, pathogens, and distinct infection pattern, had greater risk of all-cause mortality compared with those with infrequent infections. Further research to define the overall infection burden in older adults is needed for risk stratification and to inform prevention strategies. Full-Text PDF Open Access